Genomic Characterization of Extensively Drug-Resistant NDM-Producing Clinical Isolates With the Emergence of Novel .

has become a major challenge to clinicians worldwide due to its high epidemic potential and acquisition of antimicrobial resistance. This work aimed at investigating antimicrobial resistance determinants and their context in four extensively drug-resistant (XDR) NDM-producing clinical isolates collected between July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 were collected and screened for acquired carbapenemases ( , and ) using PCR. Four NDM producer isolates were identified and selected for whole-genome sequencing, multilocus sequence typing, and resistome analysis. Antimicrobial susceptibility profiles were determined using disk diffusion and broth microdilution tests. All -positive isolates were XDR. Three isolates belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570/1701 (M20) and IC9 corresponding to ST85/ST1089 (M02 and M11). For the first time, we report gene on the chromosome of an strain that belongs to sequence type ST164/ST1418. Together with , was bracketed by two copies of IS in ST85 isolates possibly facilitating co-transfer of amikacin and carbapenem resistance. A novel allele ( ) with an upstream IS element was identified in M19 (ST/CC164 and ST1418/CC234). genes harbored by M02 and M11 were uniquely interrupted by IS1008. Tn-associated was carried by M20. genes were preceded by IS element in M02 and M11. AbGRI3 was carried by M20 hosting the resistance genes (), (), , ant(3), , , (), and (). Nonsynonymous mutations were identified in the quinolone resistance determining regions ( and ) of all isolates. Resistance to colistin in M19 was accompanied by missense mutations in and genes. The current study provided an insight into the genomic background of XDR phenotype in recovered from patients in Egypt. WGS revealed strong association between resistance genes and diverse mobile genetic elements with novel insertion sites and genetic organizations.